Intelligent Manufacturing of Pharmaceutical Film Coating Using Terahertz Pulsed Imaging, Optical Coherence Tomography and Numerical Modelling

Lead Research Organisation: University of Liverpool
Department Name: Electrical Engineering and Electronics


Functional coatings are highly engineered drug delivery systems whose structure and composition is critical to the controlled release of the active pharmaceutical ingredient in the human body. This increase in manufacturing complexity coincides with a time when companies are looking to reduce costs while regulators exert pressure on the sector to ascertain a greater understanding of the products' critical quality attributes (CQAs) and associated process control. To date the development and manufacture of these high value products is challenging owning to the fact that pharmaceutical processing is complex and dominated by empirical knowledge with large gaps remaining in the full scientific understanding of the underlying processes. It is an essential need, and also a big business opportunity, to develop a step change technology-a "smart factory" capable of manufacturing these high-value products to user-defined specifications. This EPSRC call provides the consortium with the necessary funding to develop the basic components of a "smart factory" by the integration of process modeling and in-process diagnostic capability for real-time in-situ process control of advanced tablet manufacturing. By utilizing the unique diagnostic information obtained by a range of in-line sensors including our THz imaging and optical coherence tomography (OCT) sensors, we will develop theoretical models to identify key process parameters that will ultimately allow the development of an active feedback loop for advanced process control and optimisation. This EPSRC project will allow Cambridge and Liverpool University to use their combined expertise and proven technology, steered by a world leading supplier of manufacture equipment (Bosch, Liverpool, UK) and a global pharmaceutical company (Pfizer, Sandwich, UK) and supported by academia (Professor De Beer, Ghent University, Belgium), a technology SME (TeraView, Cambridge, UK) and with additional insight from the regulators (Dr Wu, FDA), to provide a highly advanced manufacturing capability currently not available to the industry.


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Description This is a joint collaborative project between Cambridge University and Liverpool University, aiming to achieve real-time in-situ process control of advanced tablet manufacturing by the integration of process modeling and in-process diagnostic capability. The sensing technology is based on terahertz (THz) and optical coherence tomography (OCT) inline sensors.

We have successfully achieved all major objectives of the project. At Liverpool we have successfully developed a compact and portable fibre-based OCT sensor and the associated data acquisition, feature extraction, and signal processing and communication algorithms suitable for in-line process monitoring applications. The developed OCT sensor, together with a THz sensor, has been successfully integrated into a lab-scale pharmaceutical coater (Cambridge University) with the inline monitoring capability demonstrated experimentally. Two peer-reviewed papers have been published in J. Pharm. Sci., and an additional one has been accepted for publication in the same journal.

The research results may lead to research impact on pharmaceutical industry and beyond. Pfizer has expressed interest in the developed technology and we have since performed two site trials at Pfizer (Sandwich, UK) although we could not perform trial measurements in other Pfizer sites outside UK because of budget and time constrains. Initial discussion with GSK (Brentford, UK) was also very encouraging.

Furthermore, we have measured 22 different common coatings, aiming to have a thorough evaluation of the applicability and capability of OCT to investigate pharmaceutical film-coated tablets. We did find that although OCT has been demonstrated to be able to directly measure the film coating thickness of pharmaceutical tablets in real-time and in a non-destructive and contactless manner, it can not be used to measure some coatings particularly these containing titanium dioxide. This 'negative' result is important for the decision maker of pharmaceutical industry and we have since submitted this work for publication in J. Pharmaceutical Science. THz sensor, on the other hand, can be used to measure all tablet coatings.

Outside pharmaceutical industry sector, the related sensing technology may also find applications in automobile industry (preliminary results have been published in Applied Optics) and medical imaging (one paper published in Optics Express). In addition, one self-funded PhD student has published two papers on plasmonic confinement and enhancement (Applied Physics Letters; Optics Express) which is related in that the same concept might be applicable for high-resolution THz and OCT imaging that may lead to new academic research and application opportunities.
Exploitation Route Bosch Packaging Technology Ltd (Liverpool, UK), one of our project partners, was very interested and planned to adopt the developed OCT and THz into their coating drum to strengthen their position as the world leading supplier of pharmaceutical manufaturing equipment. Unfortunately the Bosch headquarter in Germany has decided to close the entire UK site and this had a negative impact on the adoption of the developed technology.
Nevertheless we have secured small funds (Liverpool University EPSRC Impact Grant and EEECS School Travel grant) which will be used to cover the travel costs for site trial measurements at Pfizer and Bosch who has highly valued the developed technolgy. A local compnay also had interest to manufacture and market the product based on the developed technology. We are currently exploiting options with Liverpool University Business Gateway as how to transfer the developed technology into a product with CE marking.
Sectors Healthcare,Manufacturing, including Industrial Biotechology,Pharmaceuticals and Medical Biotechnology

Description A novel sensor for coating process monitoring
Amount £12,034 (GBP)
Organisation University of Liverpool 
Sector Academic/University
Country United Kingdom
Start 04/2016 
End 03/2017
Title High-resolution optical coherence tomography hardware and software 
Description A high-resolution OCT instrument with the data acquisition and data processing software, suitable for non-destructive evaluation of a wide range of coatings or layered structures. 
Type Of Material Technology assay or reagent 
Year Produced 2016 
Provided To Others? Yes  
Impact is helping final year project students and PhD research students from within and outside my School. 
Description Alternative ways to measure the removal process 
Organisation Unilever
Department Unilever UK R&D Centre Port Sunlight
Country United Kingdom 
Sector Private 
PI Contribution feasibility study: to apply the developed technology to study the removal of fats from substrate.
Collaborator Contribution The partner provided the test samples and also small fund to cover the ruling cost.
Impact ongoing
Start Year 2017
Title Online OCT sensor 
Description A portable optical coherence tomography (OCT) device has been developed. It has high data acquisition speed (40,000 waveforms per second) thus is well suitable for online monitoring coating process. 
Type Of Technology Systems, Materials & Instrumental Engineering 
Year Produced 2015 
Impact This device will enable real time inline process monitoring and control thus it will have a positive impact on the process analytical control (PAT) and the manufacturing of high value pharmaceutical products. 
Description Analysis of pharmaceutical coatings using optical coherence tomography 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Industry/Business
Results and Impact Delivered an invited talk at a major pharmaceutical company.
Discussed potential collaboration work.
Year(s) Of Engagement Activity 2016
Description Terahertz time-domain imaging: development and industry applications 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Industry/Business
Results and Impact Keynote at the 2016 IET Colloquium on Millimetre-wave and Terahertz Engineering & Technology, Imperial College London, UK (London, 31st March 2016)
Year(s) Of Engagement Activity 2016
Description Visitors from Industry 
Form Of Engagement Activity Participation in an open day or visit at my research institution
Part Of Official Scheme? No
Geographic Reach Regional
Primary Audience Industry/Business
Results and Impact Introduce optical coherence tomography technology to visitor from one of the largest car paint company. The company has subsequently provided some test samples and we are currently look for funding opportunities to move this forward.
Year(s) Of Engagement Activity 2015